Conditions & Diseases Affecting Sensation and Motor Control

Nancy Long Sieber, Ph.D.September 24, 2012

http://www.mymodernmet.com/profiles/blog/list?tag=eyes

Somatosensory signals ascend the spinal cord, and are relayed (via the thalamus) to the somatosensory cortex

The body is “mapped” onto the somatosensory cortex.

Control of Voluntary Movement

Lowest level: motor programs

carried out

Receptors in muscles, tendons and joints

Brain stem and Spinal cord

Sensorimotor cortex

Subcortical nuclei, including basal ganglia and thalamus

Cerebellum

Association cortex and other brain areas.

Muscle fibers

Highest level: command initiated

Middle level: motor programs

created

Lower Motor Neurons(from spinal cord to muscle) =>

UpperMotor Neurons (all motor neurons withinthe CNS) =>

Pathology at the neuromuscular junction (NMJ)

Curare

• A toxin derived from root of a local plant, used by native of the Amazon Basin to poison arrow tips.

• Synthetic derivatives are used clinically.

• An antagonist for Ach binding• Does not cross the blood-brain

barrier.• Effects are partially reversible by

neostigmine

http://www.general-anaesthesia.com/images/indian-curare.html

Myathenia gravis: a disease of the NMJ

• Symptoms: – Progressive muscle weakness– Respiratory muscle failure– Repeated contraction is particularly difficult – resembles fatigue

• Pathophysiology– An autoimmune disease – B cells make antibodies that bind to and block

the Ach receptors of the NMJ– With fewer receptors available, Ach binding is less likely

• Treatment – Mechanical ventilation– Neostigmine and related drugs – block acetylcholinesterase, – Thymectomy causes remission in about half of the cases

http://www.dana.org/news/brainhealth/detail.aspx?id=9844

Botulism Poisoning (Botulinum toxin,

from bacteria Clostridia botulinum)

• Botulinum toxin is the most toxic substance known.• Botulinum toxin is an enzyme that cleaves docking proteins

(called “snares”) off of the acetylcholine-containing vesicles, preventing its release at the neuromuscular junction and in the autonomic nervous system.

• Early symptoms include dry mouth, double vision, inability to focus eyes.

• Symmetric flaccid paralysis develops later• Patients need to be kept on a respirator for several weeks

while the axons of the nerve cells recover.

Sensory Loss:

Visual Impairment

/

Anatomy of the Visual System

http://www.kellogg.umich.edu/theeyeshaveit/anatomy/visual-pathway.html

Anatomy of the eye

http://www.thirdeyehealth.com/eye-diagram.html

Vision Problems in People (and Animals) with Albinism

• Foveal Hypoplasia - incomplete development of the fovea, the central region of the retina.

• Strabismus – eyes out of alignment (cross-eyes)

• Congenital Nystagmus – involunatary movement of the eyes

• Misrouting of the Optic Nerve

http://www.animaltalk.us/albino-animals/

Cortical Blindness• Eyes are normal, but there is damage to the visual

cortex.

• Often occurs as the result of a head injury or a stroke.

• People with this condition sometimes retain some vision.

• Even people who are completely blind from this condition may have some “blind-sightedness”.See link: http://www.the-scientist.com/blog/display/55315

The Braille Alphabet

Former Governor David Paterson of New York is legally blind. He does not read Braille, but he does have a tremendous memory.

To be legally blind, a person must have vision worse than 20/200 in their best eye, or a visual field of 20 degrees or less.

Rods and Cones are the Photoreceptors in the Retina

The cones are tuned in to one specific color - red, blue or green.

People who are color blind are deficient in one or more type of cone

Color Blindness

http://colorvisiontesting.com/ishihara.htm

Color Blindness Test

Diseases that Affect Movement and/or Sensation

But not other things, at least not all that much, or at least not at first.

Disease of Sensory and/or Motor Control

• Parkinson’s Disease – results from death of dopamine-containing neurons in the substantia nigra. Affects ability to initiate movements.

• Huntington’s Disease – involuntary movement due to loss of inhibitory cells in the basal ganglia

• Multiple Sclerosis – affects neurons in the CNS involved in sensation and movement. Some also experience mild cognitive effects.

• Guillain-Barre Syndrome – loss of myelin in the peripheral nervous system, leading to difficulty in movement

• Amyotrophic Lateral Sclerosis – affects motor neurons both in the CNS and in the periphery.

Parkinson’s Disease• Substantia nigra cells in the basal ganglia are gradually

killed off, but the mechanism of neuronal death is not known

• These cells normally synapse on cells involved in the initiation of movement.

• Patient experiences “intention tremor”, and rigidity. Movements become increasingly difficult to carry out.

• The disease shortens life expectancy. Patients become increasingly frail and immobilized. Some have trouble with swallowing. Some experience cognitive problems.

Regions of the brain affected by Parkinson’s Disease

http://www.newhopeforparkinsons.com/images/brainillustration2.gif

Huntington’s DiseaseAn autosomal dominant trait - children of an affected parent have a 50% of developing the disease.

Symptoms are caused by lossof inhibitory neurons in the basal ganglia.

http://www.brainexplorer.org/glossary/Huntingtons_disease.shtml

Multiple Sclerosis

• An autoimmune disease that leads to demyelinization of neurons in the CNS

• Patients usually present with blurred or double vision. They go on to experience abnormal sensations, and muscle weakness.

• 50% of patients need help with walking within 15 years of diagnosis.

http://www.riversideonline.com/source/images/image_popup/ww5r308_big.jpg

MS is characterized by demyelinization of neurons in the CNS

Pathogenesis of MS• In patients with MS, T lymphocytes, which are

normally excluded from the brain by the blood-brain barrier (BBB) are able to enter.

• These cells are thought to trigger the damage to myelinated neurons in the CNS.

• The cause of this opening of the BBB is unknown – it the cause of the problem, or is it just a consequence of inflammation caused by something else?

Many factors are thought to contribute to MS:

• Intrinsic problems with immune system - probably common to all autoimmune diseases, probably genetic.

• Problems with the blood-brain barrier, allowing T cells to enter the CNS and promote production of antibodies against myelin

• A specific Infectious agent – Some have proposed that a virus triggers the autoimmune response that leads to demyelinization. No specific agent has been found

• Vitamin D deficiency – the geographic distribution supports this. Vitamin D is involved in regulating the immune system, as well as neural function.

http://sofija.files.wordpress.com/2007/01/ms_worldmap.jpg

                                                                                                                                                

Grigoriadis and Hadjigeorgiou Journal of Autoimmune Diseases 2006 3:1   doi:10.1186/1740-2557-3-1

Proposed scheme for virus-mediated autoimmunity in multiple sclerosis.

http://content.revolutionhealth.com/contentimages/h9991221.jpg

MRI Images help diagnose and monitor MS

Treatments for MS• Anti-inflammatory agents – corticosteroids, chemotherapeutic

agents, etc. as used to treat lupus. – Drawbacks: These drugs have many side effects. In addition, they generally

increase the risk of infection, and viral and bacterial infections have been shown to speed the progression of MS.

• Supplemental vitamin D has been shown to slow progression

• Tysabri – A monoclonal antibody against T cells, which blocks their entry into the CNS. – Drawback: cripples brain defenses against infection. Patients are at risk of

deadly brain infections, especially progressive multifocal leukoencephalopathy (PML).

Guillain-Barre Syndrome is caused by demyelinization of peripheral nerves

• Thought to be caused by the autoimmune attack on myelin in peripheral nerves.

• Often occurs after a viral infection, or (rarely) after vaccination.

• Onset of the disease is sudden, and many patients are immediately admitted to the intensive care unit of the hospital.

• While many cases are mild, some patients experience significant weakness of the respiratory muscles, and must rely on mechanic ventilation.

• About half of the people who get Guillain-Barre recover fully within 1 year. Some have lingering weakness and numbness or tingling sensations (paresthesia).

Guillain-Barre Syndrome

http://www.monografias.com/trabajos37/sindrome-guillain-barre/Image8645.jpg

Amyotrophic Lateral Sclerosis (ALS) affects both upper (within the CNS) and lower (those that directly

innervate muscle) motor neurons.

http://len.epfl.ch/webdav/site/len/shared/import/migration/ALS1.jpg

Genetics and ALS• 5-10% of cases are strictly genetic (Familial ALS).

• Of these about 20% are due to a defect in an enzyme called superoxide dismutase 1 (SOD1), which scavenges free radicals.

• This finding has led some to speculate that free radical damage may be involved in other forms of the disease.

• The defective protein may also interfere with movement of ADP into mitochondria, interfering with ATP production.

• More recent studies have identified a defect in the gene for Ubiquilin 2, a “housekeeping” protein, as a cause of certain hereditary forms of the condition. Without this protein, damaged and misfolded proteins remain in the neuron, eventually causing neuronal death.

Possible environmental risk factors

• Exposure to a dietary toxin called BMAA may account for high incidence in Guam and other places in the western Pacific.

• US military veterans from both the Pacific and the Gulf War.

• Exposure to herbicides has long been suspected, as clusters have been seen in athletes and farmers.

Possible Mechanisms of ALS Pathogenesis

• Oxidant injury, perhaps due to some abnormality in antioxidant systems

• Glutamate toxicity, perhaps due to a defect in astroglial cells which normally remove this neurotransmitter from the synapse. The resulting “excitotoxicity” leads to neuronal death, causing further release of glutamate.

Treatments for ALS

• Riluzole, a drug that decreases glutamate release is the only FDA-approved drug for ALS. It is only moderately effective suggesting that other mechanisms are involved in the pathogenesis of ALS.

• Other drugs are used to treat symptoms of the disease, including muscle cramps, spasms, fatigue, etc.

• Physical therapy